This application is a revised competitive renewal application. The overall goal of this interdisciplinary research program is to determine the cognitive functions of cortical cholinergic inputs and their efferent and afferent neuronal circuits. This research integrates contemporary behavioral, neurochemical, and neuro physiological approaches to establish precise relationships between attentional processes and the activity of cortical cholinergic inputs and the cholinergic modulation of cortical information processing. Research conducted during the initial funding period substantiated hypotheses concerning the necessity of cortical cholinergic inputs for attention performance, the specificity of attentional performance associated changes in cortical acetylcholine (ACh) release, and performance-associated and ACh-mediated changes in cortical neuronal activity. The proposed research will continue to exploit the heuristic power of this multidisciplinary research approach in order to test hypotheses about the precise relationship between attentional performance and cortical ACh efflux, the role of prefrontal cortical (PFC) cholinergic inputs in mediating performance-associated desynchronization of PFC neuronal activity, the role of PFC cholinergic inputs in regulating attentional performance-associated changes in ACh release in the posterior parietal cortex (PPC), and the contribution of prefrontal projections to the basal forebrain to the attention performance-associated activation of the PPC. The results of this research are expected to yield a precise determination of the variables of attentional performance that activate cortical cholinergic inputs, the role of cholinergic inputs in prefrontal information processing, and to substantiate hypotheses indicating a crucial role of PFC cholinergic inputs in the performance-associated activation of the 'anterior attention system' and the resulting top-down modulation of cholinergic activity in posterior cortical regions. [unreadable] [unreadable]